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Researchers have suggested one developmental pathway of behavior problems in childhood from infant irritable temperament eliciting negative parenting behaviors (e.g., Bell, 1968; Paterson & Sanson, 1999; Patterson 1986; Rothbart & Bates, 2006). Children and infants with an irritable temperament evoke more negative or hostile reactions from both their parents (Van den Boom et al., 1994) and parents of other children (Dumas & LaFreniere, 1993). In middle childhood, an irritable temperament predicted negative parenting, and negative parenting predicted behavior problems, although these variables were not fully prospectively assessed (Lengua & Kovacs, 2005). The present study improves on prior studies by using a fully prospective design. To do so, we used a subset of data from a large, nationally representative sample of mothers and their offspring. We first hypothesized that infant irritable temperament would predict externalizing behavior problems in mid-childhood. Second, we hypothesized that negative parenting practices (e.g., lack of maternal warmth, lack of learning stimulation, and harsh practices) would mediate the relationship between infant temperament and externalizing behaviors. Finally, we tested this mediation model both between families and within families, as a sibling comparison. Results indicated that maternal warmth and lack of learning stimulation mediated the relationship between infant temperament and behavior problems between families, but not within. Specifically, within families, infants with an irritable temperament evoked lower levels of maternal responsive, but these lower levels of responsiveness were not predictive of behavior problems. Regarding learning stimulation, neither step of the mediation was significant within families. Finally, harsh parenting did not mediate the relationship between temperament and behavior problems within or between families. However, within families, harsh parenting predicted later behavior problems. These findings suggest that passive gene-environment correlations account for much of the variation observed between families in the role of temperament and parenting in the development of behavior problems.